Over 10,000 years ago, humans began to domesticate animals. Livestock-sheep, goats, and cattle in Southwest Asia, pigs in current-day China-began to replace hunting as the primary source for meat and skins. Humans found new uses for animals: collecting milk from lactating ruminants and eggs from poultry; harnessing cattle, donkeys, and water buffalo to plows; shearing the wool from sheep and alpacas; climbing onto the backs of horses and camels for personal transportation; and, of course, producing biopharmaceuticals using proteins extracted from the milk of transgenic goats.

If that last item sounds a bit abrupt in the chronology of animal domestication, that's because it is. Even after thousands of years of selective breeding, farmers and animal science researchers in the 20th century found plenty to improve upon. The establishment of new and enhanced livestock breeds moved at an astonishingly rapid pace, as developments that might have taken centuries were accomplished in decades. Yet, while modern farmers and researchers possessed tools unavailable to their forbears, they still relied on selective breeding to achieve genetic upgrades.

In the 1980s, the advent of recombinant DNA technology appeared to herald a new age in animal agriculture, allowing the engineering of specific genes and selective introduction of novel traits. Scientists began creating transgenic animals that served as better lab subjects, (such as "knockout mice," engineered not to express a certain gene); enhanced animal-generated biotherapeutics (such as pharmaceutical proteins from sheep's milk, first at Roslin Institute in 1989); could potentially develop into future organ donors (usually attempts at pigs modified to grow specific organs compatible for transplant into humans); and even novelty pets (starting with the fluorescent GloFish).

This period also marks when researchers began attempting to apply germ-line engineering to improve animals' food production. Unlike other types of transgenic technologies, most of which aim to adapt animals for novel uses, attempts to upgrade livestock-based food production through transgenics pits genetic engineering against the time-tested mechanisms of selective breeding that had gradually honed those same characteristics over millennia. Humans have been developing specialized varieties of sheep for at least six to eight thousand years, selecting for some of the same traits-fast growth rates, feed conversion efficiency-that the Roslin Institute has tried, mostly in vain, to improve through genetic engineering.

Meanwhile, when other researchers at Roslin began engineering transgenic sheep that produce biotherapeutic proteins in their milk, they were attempting something that couldn't be done through conventional methods. And unlike bioengineered food animals, "pharming" reached the market and is being adopted in new forms. GTC?Biotherapeutics (see page 11) was the first to get regulatory approval for a pharmaceutical produced by a transgenic animal with ATryn, an antithrombrin derived from the milk of transgenic goats. Other companies have since developed goats, cows, and even rabbits that can produce various therapeutic proteins in their milk. The end product may not be novel, but the means certainly is. Most of the biotherapeutics being produced through animal pharming are already commercially available through other production means, but the strength of pharming is its potential to manufacture the same product at a significantly lower cost. A few hundred of GTC's goats can produce as much antithrombrin proteins as a lab that costs millions of dollars to set up and millions more to scale up.

The same cannot always be said of transgenic food animals. In many cases, germ-line engineering of a food-producing animal may be used to attempt to extend the aims of conventional breeding; in other words, to improve food production. These traits can be improved without genetic engineering, of course, and have been for thousands of years, but genetic interventions can produce much more drastic results-for better or worse. AquaBounty's genetically modified salmon grows far more rapidly than its conventional counterpart, and although this "improvement" raises a host of serious concerns (detailed by Eric Hoffman on page 6), from a strictly production-oriented standpoint, it could be a boon to some fish farmers (and certainly to AquaBounty). On the other hand, when the United States Department of Agriculture funded the development in the 1980s of pigs carrying the human growth hormone in an attempt to create a faster growing, leaner meat animal, the results yielded only a sickly litter afflicted with an array of odd conditions, including pneumonia, peptic ulcers, and arthritis. Of the 19 now-infamous "Beltsville pigs," 17 died before reaching one year of age.

These ventures may have resulted in an animal welfare fiasco and the very real threat of a catastrophic disruption of ocean ecosystems, but we can at least see why they were carried out. The achievement-or intent, in the Beltsville pigs' case-was to more efficiently convert grain to meat, doing so with one radical improvement that may have taken many years to accomplish through conventional breeding.

Many other endeavors to improve livestock food production through germ-line engineering appear redundant or superfluous, which may explain their tendency to either fail or fizzle out. Ironically, many of these projects also receive the most press, if only for their novelty:

"Enviropig," developed by researchers at Ontario's University of Guelph, is able to digest a form of phosphorous in feed grains that it would normally excrete, reducing the phosphorous levels of its manure by 30 to 70%, with the aim of diminishing the environmental impact of large-scale hog production.

Akira Iritani, a scientist at Japan's Kinki University, reported in 2002 that his team was the first to successfully add a functioning plant gene to an animal, in the form of pigs that carried a spinach gene. As a result, Iritani said, the pigs' carcass held 20% less saturated fat, converted by the novel gene into linoleic acid.

In the 1990s, British researchers began attempts to develop transgenic sheep resistant to scrapie, a prion disease similar to bovine spongiform encephalitis (or mad cow disease), which is 100% fatal in sheep. Research has also been undertaken to develop cows resistant to mad cow disease, so far with no published success.

The prevailing flaw in these technologies-presuming they were successfully developed-is that while the method may be novel, the result is not. A surprising amount of research on transgenic food animals has been bent on achieving what can already be accomplished more gracefully through conventional breeding, altered production practices, or human behavioral adjustments. In many cases, all of the time and money spent developing a new transgenic livestock breed serves only to replace an existing solution, even if it is more efficient, effective, and sustainable than a genetically engineered silver bullet.

Take the above examples:

"Enviropig" is awaiting approval for human consumption in Canada and the U.S., and already has the green light from Canada's Department of the Environment and the blessing of swine industry groups. Yet, it represents an incomplete solution (phosphorous is not the only problem nutrient in pig manure) to a problem that already has solutions at hand. Unfortunately, those alternatives-changing the pigs' rations by adding an enzyme (phytase, which can reduce phosphorous in manure by over 50%) or using different grains; being more careful and strategic when spreading manure on fields as fertilizer; and most of all, ditching the vast 10,000+ hog confinement operations in favor of smaller, diversified farms-require behavioral changes in the hog industry, as opposed to maintaining the status quo with new pigs. Enviropig has been framed by its creators and the swine industry as an environmental breakthrough, but from the perspective of environmental protection, it addresses a problem that already had known solutions. In reality, despite the name, Enviropig was designed to solve hog industry problems. It reduces the amount that producers need to spend on mineral supplements, but more importantly, it allows the hog industry to appease regulators and scale up operations without changing the prevailing practices.

Iritani's "Popeye pig," with apparently 20% of its saturated fat converted to healthier unsaturated fats by an inserted spinach gene, never resurfaced after it was announced in 2002. At the time, Iritani essentially admitted that he did not expect the pig to be commercialized due to lack of public acceptance; but he also expressed his hope that "safety tests will be conducted to make people feel like eating the pork for the sake of their health." The notion of encouraging people to eat pork for their health may raise an eyebrow; beyond that, one need not think too hard to come up with simpler ways to cut down on saturated fat (trim it off of your pork chop, or simpler yet, cut back on the meat).

Attempts to engineer transgenic scrapie-resistant sheep appear to have fallen by the wayside, presumably because many sheep already carry a dominant gene for scrapie resistance, allowing producers, after sending biopsies to a lab, to select against scrapie susceptibility. Mandatory scrapie ID tags in the U.S. and other countries have also helped track and control the spread of scrapie. The best argument that conventional breeding and well-executed containment practices preempt any usefulness of transgenic scrapie-resistant sheep is their success: Australia and New Zealand have officially eradicated the disease, and the U.S. has reduced it to 0.03% of the nation's entire flock.

Like transgenic scrapie resistance, genetically altering cows' genomes to grant them mad cow resistance is essentially a superfluous advance. While some research suggests that genes can influence mad cow resistance or susceptibility, the disease is most often believed to be contracted when brain tissue from another animal mad cow disease carrier (or scrapie, some studies say) enters into a cow's feed. In the U.S. and Canada, stringent steps to keep ruminant tissue out of ruminant feeds helped essentially eradicate mad cow in North America-no transgenic influence needed.

Despite the headlines about cows that produce something akin to human breast milk or cattle genetically engineered for immunity to sleeping sickness, the most marked shortcoming of transgenesis as a means of improving food animals is evidenced by the host of experiments that don't make headlines. Attempts to create healthy, fast-growing transgenic sheep carrying the human growth hormone began in the mid 1980s. In early experiments, the transgenic lambs grew at average rate until reaching 15 to 17 weeks, at which point "over expression" of the growth hormone resulted in two rather counterproductive side effects: "reduced growth rate and shortened life span." Fifteen years later, growth hormone experiments in sheep had only managed to yield larger than normal sheep. At 12 months, transgenic rams were only 8% larger than the control rams, and with no significantly increased feed efficiencies noted.

AquaBounty's success bringing genetically modified salmon to market is, so far, an anomaly; to date, no other animal has been commercialized carrying a transgene that increases the amount of food it produces or the efficiency with which it converts feed to meat, milk, or eggs. Meanwhile, the goats, cows, chickens, and even rabbits that have been developed to produce human biopharmaceuticals are, in some cases, already proving to be the most economical producers of some therapeutic proteins. Pharming is not without its drawbacks, and the need to carefully test and regulate all products of transgenic animals is evident. Nonetheless, if a genetically modified animal is to deliver significant benefits for humans, there certainly seems to be a surer path for those using genetic engineering to coax an entirely new use out of an animal which has been selected on the basis of its existing advantageous traits; as opposed to those projects taking on conventional breeding programs at their own game-attempting, with a single transgenic silver bullet, to outshine thousands of years of purposeful selection.